I. What every physician needs to know.

Hashimoto's thyroiditis is an autoimmune inflammatory disorder of the thyroid gland. It is also referred to as chronic lymphocytic thyroiditis or chronic autoimmune thyroiditis. The synonyms of this disease are derived from its pathological features which include diffuse lymphocytic infiltration of the thyroid gland, first described by Hashimoto in 1912, and the presence of autoantibodies against thyroid antigens.

It is the most common cause of hypothyroidism in the developed world and is more prevalent among women. Frequently, due to a progressive loss of thyroid function, these patients have features of hypothyrodism on presentation and can have associated goiter formation. Rarely, you may see patients who have a clinical picture of hyperthyrodism as an initial presentation due to rapid thyroid hormone release in the presence of significant thyroid gland T cell mediated destruction.

Given the prevalence of the disease in regions that do not have iodine deficiency, any case of subclinical hypothyrodism should raise our suspicion for Hashimoto's. These patients can also present with features of hypothyroidism. Hashimoto's thyroditis should be suspected if a patient has an elevated thyroid-stimulating hormone (TSH) and presence of thyroid antibodies. Rarely in the initial phase of the disease a patient can have features of hyperthyrodism referred to as Hashitoxicosis due to rapid destruction of the gland and release of hormones.

A. History Part I: Pattern Recognition:

A typical patient would be an older woman with features of hypothyrodism including a diffusely enlarged thyroid gland, listed below. Rarely, you might have a patient who presents with painful gioter. Common complaints at the time of presentation include:

B. History Part 2: Prevalence:

Hoshimoto's is the most common cause of hypothyrodism in the developed world when there is no iodine insufficiency. It has an incidence of 4/1000 women. The disease has a female preponderance ranging from 5-9 times based on various literature. It is seen more often in the Caucasian population than the African American population. The risk of Hashimoto's thyroiditis presenting with hypothyrodism also increases with age, with average age of 60 years at the time of presentation.

Amongst pregnant patients, some can go on to develop post-partum thyroiditis from 1-6 months post delivery. The theories for postpartum thyroiditis range from immune suppresion in pregnancy, to changes in cytokines due to increased progesterone to a pre-existing thyroiditis or thyroid insufficiency becoming unmasked by the stress of pregnancy. Twenty-five to fifty percent of these patients can develop Hashimoto's thyroiditis later in life.

There are specific environmental exposures that increase the risk of this disease. There is insufficient data to state that radiation exposure increases the risk of Hashimoto's thyroditis.

There is data to support a genetic link to hashimoto's thyroiditis such as HLA -DR polymorphisms or genes CTLA-4 and PTPN22 that are associated with both Hashimoto's thyroiditis and Graves' Disease. However at the current time there is no genetic test that can be offered to diagnose Hashimoto's.

There does appear to be an increased incidence of the disease within families that have a member diagnosed with Hashimoto's. There is also an increased incidence seen in patients withTurner's and Down's syndrome.

There is an association between Hashimoto's thyroditis and other autoimmune thyroid diseases with some autoimmune conditions. These include type 1 diabetes mellitus, pernicious anemia, vitiligo and Addison's disease.

There is no evidence to associate any viral or bacterial infection to Hashimoto's thyroditis in the adult patient.

The increased incidence of Hashimoto's in developed coutries is associated with increased iodine supplementation as well. There is need for additional data to see if an association with selenium deficiency exists as well.

C. History Part 3: Competing diagnoses that can mimic Hoshimoto's thyroiditis.

) Multinodular Goiter: can be distinguished by thyroid ultrasound with Hashimoto's frequently having a heterogenous appearance on ultrasound.

) Thyroid cancer: if clinical suspicion is high or if patient has an asymetrical enlargement of one nodule, there is a need for FNA to rule out thyroid lymphoma; there is some literature that raises the concern for papillary carcinoma of the thyroid with Hashimoto's but there is insufficient data at this time to conclusively associate the 2 diseases.

D. Physical Examination Findings.

These patients often present with features of hypothyroidism, as listed below, or can also have goiter formation (rarely painful goiter):

E. What diagnostic tests should be performed?

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Positive thyroid antibodies are needed to establish the diagnosis. Anti-TPO are positive in 90-100% of patients with Hashimoto's and Anti-TG in 65%. Follow the following order in diagnositic testing:

) TSH (will often be elevated)

) Free T4 (which can be decreased or normal as in the case for subclinical hypothyrodism)

) Anti-TPO antibody

) Anti-TG antibody

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Consider ultrasound of the thyroid if the patient also has a dominant thyroid nodule or appearance of a multinodular lesion and proceed with work-up. Features of Hashimoto's thyroiditis on ultrasound include:

Hypoechogenicity

Heterogeneous appearance of thyroid

Numeroud pseudonodules

Diffuse cystic changes

Septa formation

Presence of lymph node which is non-malignant in appearance

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Twenty-four-hour radioactive iodine uptake is not required in the diagnosis of this disease as a routine. Free T3 is routinely ordered with Free T4 and is of no diagnostic use.

III. Default Management.

The decision to treat Hashimoto's thyroditis is to be based on symptoms and complications:

) Given that Hashimoto's thyroiditis can present with subclinical hypothyroidism, the decision to treat should be based on the clinical considerations. If the patient is pregnant, infertile or trying to conceive, should be started on thyroid hormone replacement. There is insufficient data to recommend treating all cases of subclinical hypothyroidism associated with Hashimoto's. While some patients may have mild improvement of symptoms, overall mortality or quality of life indicators do not seem to improve in this scenario.

) Treatment of hypothyroidism associated with Hashimoto's after evaluation as above and begins with initiation of levothyroxine and monitoring of response and reassessment in 4-6 weeks.

A. Immediate management.

) Electrocardiogram (EKG) to assess for any arrhythmias or any signs of acute coronary syndromes (ACS)

) Assessment and treatment of congestive heart failure (CHF)

) Decision to start levothyroxine will need to be made based on above during hospital course

B. Physical Examination Tips to Guide Management.

) Thyroid exam to ensure that the thyroid gland is not rapidly enlarging in size which might indicate further evaluation either for malignancy or a hemorrhagic component.

) Assess for any change in voice or SOB to see if patient has compressive features of thyroid enlargement and possible need for surgical intervention.

) Cardiovascular exam for arrhythmias either due to the disease or due to overtreatment of disease, this can trigger arrhythmias as well. Assessment for heart failure and ACS especially in patients who present with over hypothyroidism in association with Hashimoto's.

In the elderly patients start with low dose levothyroxine replacement at 25mcg daily and uptitrate every 4-6 weeks by 25mcg to have the TSH range in the high normal range. A patient who is pregnant may have increased needs for replacement during pregnancy if they are already diagnosed with Hashimoto's. Subclinical hypothyrodism in the pregnant patient is also to be treated.

TSH will need to be measured 4-6 weeks after initiation of treatment for Hashimoto's thyroiditis to see if medication adjustment is required.

D. Long-term management.

The patient will need to have their TSH monitored and increments in their levothyroxine dose will need to be made every 4-6 weeks based on their TSH and symptoms.

In a young patient who has complete destruction of the thyroid gland they can be started on 1.6 mcg/kg body weight (between 100-150 mcg) of levothyroxine and close monitoring of TSH.

E. Common Pitfalls and Side-Effects of Management

Patients with active cardiac issues need to be cautiously started on levothyroxine. There is no contraindication to therapy but it would be better to start slowly and increase the dose based on TSH. There is insufficient evidence to justify loading these patients as this might trigger arrhythmias or increase cardiac workload in a patient who already has cardiac dysfunction.

IV. Management with Co-Morbidities

N/A

A. Renal Insufficiency.

No change in management.

B. Liver Insufficiency.

Patients with compensated liver disease have an elevated free T4 due to an elevated plasma thyroid binding globulin with a high normal TSH. The free T3 level is often normal and can be elevated in the setting of acute viral hepatitis.

No change in management.

C. Systolic and Diastolic Heart Failure

Patients with hypothyrodism can have diastolic dysfunction and if left untreated progress to heart failure. In overt heart failure in a newly diagnosed hypothyroid patient consider starting levothyroxine between 25-50mcg, then based on clinical response the dose can be uptitrated in 4-6 weeks.

D. Coronary Artery Disease or Peripheral Vascular Disease

Patients with hypothyrodism and Hashimoto's thyroiditis are at increased risk for acute coronary syndrome related to increased peripheral vascular resistance, endothelial dysfunction, diastolic dysfunction and hyperlipidemia. These patients need to be initated on levothyroxine between 25-50mcg daily and titrated based on clinical response in 4-6 weeks.

E. Diabetes or other Endocrine issues

Patients with type 1 diabetes should have regular screening for thyroid disease and based on results for Hashimoto's thyroiditis given the high prevalence of the disease in the Unitied States.

F. Malignancy

Hashimoto's thyroiditis in associated with an increased risk of thyroid lymphoma (non hodgkins lymphoma). A patient with increased size of the gland, asymmetrical enlargement or associated B symptoms (20% of NHL can have symptoms of fevers, nightsweats or weight loss) should be evaluated for lymphoma and this includes an ultrasound guided fine-needle aspiration (FNA).

G. Immunosuppression (HIV, chronic steroids, etc).

Patients with HIV do not have an increased prevalence of Hashimoto's disease. However patients on HAART who are admitted with HIV related or unrelated issues may have abnormal thyroid function tests including elevated free T4 and normal TSH.

H. Primary Lung Disease (COPD, Asthma, ILD)

No change in management.

I. Gastrointestinal or Nutrition Issues

There is some data associating celiac disease with autoimmune thyroid disease. If your patient has issues or features of malabsorption, consider evaluation for celiac disease. In addition due to malabsorption they might need higher doses of levothyroxine to treat their hypothyroidism. Patients on proton pump inhibitors may have poor absorption of their levothyroxine and the 2 medications should be taken at a minimum of 2 hours apart.

J. Hematologic or Coagulation Issues

Anemia can be seen with hypothyrodism and as TSH normalizes and the patient is adequately treated, this does resolve, unless the patient has underlying iron deficiency or pernicious anemia.

K. Dementia or Psychiatric Illness/Treatment

) Neurologic changes related to hypothyrodism could improve with time once thyroid replacement is initiated if no other underlying disease process is present.

) There is a rare form of encephalopathy referred to as Hashimoto's encephalopathy, or steroid responsive encephalopathy, associated with autoimmune thyroiditis which features of encephalopathy such as psychosis, decreased cognition, depression, myoclonic jerks or depression, and positive thyroid autoantibodies. These patients may not have Hashimoto's thyroiditis or any thyroid disease and there have been reports of Grave's disease in some of these patients. Some have been shown to respond to therapy with high dose steroids and there is still much to be delineated in the pathophysiology of the disease.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

A patient with previously undiagnosed or untreated hypothyrodism could develop myxedema coma. The patient could have changes in mental status or arrthymias.

B. Anticipated Length of Stay.

A patient who has no other complication such as arrythmia would expect to have a length of stay of 2-3 days while diagnostic tests and treatment are initiated.

C. When is the Patient Ready for Discharge.

Once the patient is initiated on thyroid replacement hormone therapy and has follow-up, as long as they do not have complications such as arrhythmias, pericardial effusions or encephalopathy, they can be discharged. The patient should also be advised that any increase in the size of their thyroid gland would require an earlier evaluation.

Instructio

D. Arranging for Clinic Follow-up

The patient should be followed by their primary care physician (PCP) in 4-6 weeks with repeat testing to assess response to therapy.

1. When should clinic follow up be arranged and with whom.

The patient should be followed by their PCP in 4-6 weeks with repeat testing to assess response to therapy. They can also be established with an endocrinologist if they should have unusual presentations such as an enlarging single nodule. Any asymmetric or large increase in the size of their thyroid gland warrants early evaluation with imaging, possible radionuclide iodine uptake scan and FNA.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

TSH and a free T4

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

TSH to allow for planning for titration of levothyroxine.

E. Placement Considerations.

If a patient has psychosis or profound weakness as a result of their hypothyrodism they would need to be placed in a skilled nursing facility (SNF) to get a physical therapist (PT). This needs to be based on the initial evaluation of patient and would require PT being involved early as long patient is hemodynamically stable.

A straight forward patient with hypothyrodism related to Hashimotos's thyroiditis should not require SNF placement.

F. Prognosis and Patient Counseling.

These patients should be advised on the need to stay on their thyroid replacement therapy. The resolution of symptoms take time and symptom recurrence might not occur until the levothyroxine is missed for days to weeks. Patient should be advised not to stop the medication just because they feel better. The need for follow-up should be re-inforced. They should be advised that older patients with Hashimoto's can develop Non Hodgkin's B-Cell lymphoma over time and need to be monitored by their PCP.

VI. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation.

None

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Fall precautions if the patient is debilitated or weak on presentation. There are some who believe that there is an association between Hashimoto's and other autoimmune thyroid diseases and antiphospholipid syndrome. However, there is insufficient evidence and no consensus at this time to draw any conclusions. Therefore provide deep vein thrombosis prophylaxis for your patient based on their medical risk. Ensure that the patient has a scheduled follow-up with their PCP at the time of discharge.

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